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| | Combretastatin A4 disodium phosphate Basic information |
| Product Name: | Combretastatin A4 disodium phosphate | | Synonyms: | Combrestatin A4 3'-O-Phosphate (sodium salt);Fosbretabulin disodiuM (CA4P);CoMbretastatin A4 Phosphate(CA4P);Phenol, 2-methoxy-5-[(1Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]-, 1-(dihydrogen phosphate), sodium salt (1:2);2-Methoxy-5-[(1Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl disodium phosphate;Combretastatin A4 phosphate disodium;SODIUM (Z)-2-METHOXY-5-(3,4,5-TRIMETHOXYSTYRYL)PHENYL PHOSPHATE;Combretastatin A-4 phosphate | | CAS: | 168555-66-6 | | MF: | C18H19O8P.2Na | | MW: | 440.29 | | EINECS: | 1312995-182-4 | | Product Categories: | Aromatics;Intermediates & Fine Chemicals;Inhibitors;Pharmaceuticals;Phosphorylating and Phosphitylating Agents;Inhibitors,Pharmaceuticals;All Inhibitors;Combretastatin | | Mol File: | 168555-66-6.mol |  |
| | Combretastatin A4 disodium phosphate Chemical Properties |
| Melting point | 238-242 ºC | | storage temp. | -20°C | | solubility | H2O: soluble5mg/mL, clear | | form | powder | | color | white to beige | | InChIKey | VXNQMUVMEIGUJW-XNOMRPDFSA-L | | CAS DataBase Reference | 168555-66-6 |
| WGK Germany | 3 | | HS Code | 2919.90.3000 |
| | Combretastatin A4 disodium phosphate Usage And Synthesis |
| Chemical Properties | White Solid | | Biological Activity | fosbretabulin (combretastatin a4 phosphate (ca4p)) disodium is a microtubule destabilizing drug, a water-soluble prodrug of combretasain a4(ca4) and a tumor vascular-targeting agent.microtubule is the cylindrical and filamentous structure that required for cell shape, migration, cilia and flagella mobility etc. tubulin is the major component of microtubulesin proliferative endothelial cells, ca4p (dose less than 1/10 of the max. tolerated dose) leaded to tumor vascular shutdown, and short drug exposure of ca4p caused significant long-term anti-proliferative and cytotoxic effects. [1] in ca40 treated endothelia cell, myosin light chain was phosphorylated and lead to actinomyosin contractility, assembly of actin stress fibers and focal adhesions formation. [2] in huvec cells, ca4p blocked growth factor–induced endothelial cell proliferation and migration and impaired capillary tube formation. [3]in c57bl/6 mice, ca4p treatment in combination with mab against ve-cardherin facilitated b16 melanoma tumor necrosis and inhibited tumor neoangionesis. [3] in human breast cancer models in vivo, 6 hours after ca4p administration showed a 93% decreased functional vascular volume and lasted over the next 12 hours. [1] | | Biochem/physiol Actions | Fosbretabulin disodium (Combretastatin A4 phosphate, CA4P) is a potent vascular-disrupting agent (VDA). Fosbretabulin disodium is a prodrug that is converted to combretastatin A (Sigma Cat No. C7744) inside the endothelial cells that line blood vessels, where it binds to tubulin dimers and prevents microtubule polymerization, resulting in mitotic arrest and apoptosis in endothelial cells. Fosbretabulin disodium is a potent anti-cancer agent that exhibits antivascular effects on tumor vasculature, inducing a rapid reduction in tumor blood flow and a concomitant increase of cellular necrosis. Some of its activity is believed to involve interference with vascular endothelial-cadherin signaling in addition to its microtubule-disrupting activity. | | references | [1] dark gg, hill sa, prise ve, tozer gm, pettit gr, chaplin dj. combretastatin a-4, an agent that displays potent and selective toxicity toward tumor vasculature. cancer res. 1997 may 15;57(10):1829-34.
[2] kanthou c, tozer gm. the tumor vascular targeting agent combretastatin a-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells. blood. 2002 mar 15;99(6):2060-9.
[3] vincent l, kermani p, young lm, cheng j, zhang f, shido k, lam g, bompais-vincent h, zhu z, hicklin dj, bohlen p, chaplin dj, may c, rafii s. combretastatin a4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling. j clin invest. 2005 nov;115(11):2992-3006. |
| | Combretastatin A4 disodium phosphate Preparation Products And Raw materials |
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